scholarly journals Depletion of resident muscle stem cells negatively impacts running volume, physical function, and muscle fiber hypertrophy in response to lifelong physical activity

2020 ◽  
Vol 318 (6) ◽  
pp. C1178-C1188 ◽  
Author(s):  
Davis A. Englund ◽  
Kevin A. Murach ◽  
Cory M. Dungan ◽  
Vandré C. Figueiredo ◽  
Ivan J. Vechetti ◽  
...  
Keyword(s):  
Physical Activity ◽  
Skeletal Muscle ◽  
Physical Function ◽  
Satellite Cell ◽  
Muscle Fiber ◽  
Satellite Cells ◽  
Cell Depletion ◽  
Muscle Adaptation ◽  
Adult Skeletal Muscle

To date, studies that have aimed to investigate the role of satellite cells during adult skeletal muscle adaptation and hypertrophy have utilized a nontranslational stimulus and/or have been performed over a relatively short time frame. Although it has been shown that satellite cell depletion throughout adulthood does not drive skeletal muscle loss in sedentary mice, it remains unknown how satellite cells participate in skeletal muscle adaptation to long-term physical activity. The current study was designed to determine whether reduced satellite cell content throughout adulthood would influence the transcriptome-wide response to physical activity and diminish the adaptive response of skeletal muscle. We administered vehicle or tamoxifen to adult Pax7-diphtheria toxin A (DTA) mice to deplete satellite cells and assigned them to sedentary or wheel-running conditions for 13 mo. Satellite cell depletion throughout adulthood reduced balance and coordination, overall running volume, and the size of muscle proprioceptors (spindle fibers). Furthermore, satellite cell participation was necessary for optimal muscle fiber hypertrophy but not adaptations in fiber type distribution in response to lifelong physical activity. Transcriptome-wide analysis of the plantaris and soleus revealed that satellite cell function is muscle type specific; satellite cell-dependent myonuclear accretion was apparent in oxidative muscles, whereas initiation of G protein-coupled receptor (GPCR) signaling in the glycolytic plantaris may require satellite cells to induce optimal adaptations to long-term physical activity. These findings suggest that satellite cells play a role in preserving physical function during aging and influence muscle adaptation during sustained periods of physical activity.

scholarly journals Depletion of resident muscle stem cells inhibits muscle fiber hypertrophy induced by lifelong physical activity

2019 ◽  
Author(s):  
Davis A. Englund ◽  
Kevin A. Murach ◽  
Cory M. Dungan ◽  
Vandré C. Figueiredo ◽  
Ivan J. Vechetti ◽  
...  
Keyword(s):  
Physical Activity ◽  
Skeletal Muscle ◽  
Physical Function ◽  
Satellite Cell ◽  
Muscle Fiber ◽  
Satellite Cells ◽  
Muscle Growth ◽  
Free Access ◽  
Running Wheel ◽  
Hypertrophic Growth

AbstractBackgroundA reduction in skeletal muscle stem cell (satellite cell) content with advancing age is thought to directly contribute to the progressive loss of skeletal muscle mass and function with aging (sarcopenia). However, we reported that the depletion of satellite cells throughout adulthood did not affect the onset or degree of sarcopenia observed in sedentary old mice. The current study was designed to determine if lifelong physical activity would alter the requirements for satellite cells during aging.MethodsWe administered vehicle or tamoxifen to adult (5 months old) female Pax7-DTA mice for 5 consecutive days to effectively deplete satellite cells. Following a 2-month washout period, mice were assigned to physically active (free access to a running wheel) or sedentary (locked running wheel) conditions. Thirteen months later, at a mean age of 20 months, mice were sacrificed for subsequent analysis.ResultsSatellite cell depletion throughout adulthood negatively impacted physical function and limited muscle fiber hypertrophy in response to lifelong physical activity. To further interrogate these findings, we performed transcriptome-wide analyses on the hind limb muscles that experienced hypertrophic growth (plantaris and soleus) in response to lifelong physical activity. Our findings demonstrate that satellite cell function is muscle type-specific; fusion with fibers is apparent in oxidative muscles, while initiation of Gαi2 signaling appears to require satellite cells in glycolytic muscles to induce muscle growth..ConclusionsThese findings suggest that satellite cells, or their secretory products, are viable therapeutic targets to preserve physical function with aging and promote muscle growth in older adults who regularly engage in physical activity.

scholarly journals Starring or Supporting Role? Satellite Cells and Skeletal Muscle Fiber Size Regulation

Physiology ◽  
2018 ◽  
Vol 33 (1) ◽  
pp. 26-38 ◽  
Author(s):  
Kevin A. Murach ◽  
Christopher S. Fry ◽  
Tyler J. Kirby ◽  
Janna R. Jackson ◽  
Jonah D. Lee ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Extracellular Matrix ◽  
Satellite Cell ◽  
Muscle Fiber ◽  
Satellite Cells ◽  
Skeletal Muscle Fiber ◽  
Cell Depletion ◽  
Loss Of Function ◽  
Adult Mice ◽  
Fiber Size

Recent loss-of-function studies show that satellite cell depletion does not promote sarcopenia or unloading-induced atrophy, and does not prevent regrowth. Although overload-induced muscle fiber hypertrophy is normally associated with satellite cell-mediated myonuclear accretion, hypertrophic adaptation proceeds in the absence of satellite cells in fully grown adult mice, but not in young growing mice. Emerging evidence also indicates that satellite cells play an important role in remodeling the extracellular matrix during hypertrophy.

scholarly journals Satellite Cell Depletion Disrupts Transcriptional Coordination and Muscle Adaptation to Exercise

Function ◽  
2020 ◽  
Vol 2 (1) ◽  
Author(s):  
Davis A Englund ◽  
Vandré C Figueiredo ◽  
Cory M Dungan ◽  
Kevin A Murach ◽  
Bailey D Peck ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Satellite Cell ◽  
Satellite Cells ◽  
Gene Networks ◽  
Wheel Running ◽  
Skeletal Muscle Regeneration ◽  
Rna Seq ◽  
Muscle Adaptation ◽  
Hypertrophic Growth ◽  
Adaptation To Exercise

Abstract Satellite cells are required for postnatal development, skeletal muscle regeneration across the lifespan, and skeletal muscle hypertrophy prior to maturity. Our group has aimed to address whether satellite cells are required for hypertrophic growth in mature skeletal muscle. Here, we generated a comprehensive characterization and transcriptome-wide profiling of skeletal muscle during adaptation to exercise in the presence or absence of satellite cells in order to identify distinct phenotypes and gene networks influenced by satellite cell content. We administered vehicle or tamoxifen to adult Pax7-DTA mice and subjected them to progressive weighted wheel running (PoWeR). We then performed immunohistochemical analysis and whole-muscle RNA-seq of vehicle (SC+) and tamoxifen-treated (SC−) mice. Further, we performed single myonuclear RNA-seq to provide detailed information on how satellite cell fusion affects myonuclear transcription. We show that while skeletal muscle can mount a robust hypertrophic response to PoWeR in the absence of satellite cells, growth, and adaptation are ultimately blunted. Transcriptional profiling reveals several gene networks key to muscle adaptation are altered in the absence of satellite cells.

scholarly journals Muscle satellite cells adopt divergent fates

2004 ◽  
Vol 166 (3) ◽  
pp. 347-357 ◽  
Author(s):  
Peter S. Zammit ◽  
Jon P. Golding ◽  
Yosuke Nagata ◽  
Valérie Hudon ◽  
Terence A. Partridge ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Satellite Cell ◽  
Satellite Cells ◽  
Muscle Regeneration ◽  
Cell Phenotype ◽  
Proliferating Cells ◽  
Cell Compartment ◽  
Adult Skeletal Muscle ◽  
Muscle Stem Cells ◽  
Cell Pool

Growth, repair, and regeneration of adult skeletal muscle depends on the persistence of satellite cells: muscle stem cells resident beneath the basal lamina that surrounds each myofiber. However, how the satellite cell compartment is maintained is unclear. Here, we use cultured myofibers to model muscle regeneration and show that satellite cells adopt divergent fates. Quiescent satellite cells are synchronously activated to coexpress the transcription factors Pax7 and MyoD. Most then proliferate, down-regulate Pax7, and differentiate. In contrast, other proliferating cells maintain Pax7 but lose MyoD and withdraw from immediate differentiation. These cells are typically located in clusters, together with Pax7−ve progeny destined for differentiation. Some of the Pax7+ve/MyoD−ve cells then leave the cell cycle, thus regaining the quiescent satellite cell phenotype. Significantly, noncycling cells contained within a cluster can be stimulated to proliferate again. These observations suggest that satellite cells either differentiate or switch from terminal myogenesis to maintain the satellite cell pool.

scholarly journals Brain-derived Neurotrophic Factor Regulates Satellite Cell Differentiation and Skeltal Muscle Regeneration

2010 ◽  
Vol 21 (13) ◽  
pp. 2182-2190 ◽  
Author(s):  
Charlene Clow ◽  
Bernard J. Jasmin
Keyword(s):  
Skeletal Muscle ◽  
Satellite Cell ◽  
Satellite Cells ◽  
Neurotrophic Factor ◽  
Cell Function ◽  
Brain Derived Neurotrophic Factor ◽  
Postnatal Growth ◽  
Adult Skeletal Muscle

In adult skeletal muscle, brain-derived neurotrophic factor (BDNF) is expressed in myogenic progenitors known as satellite cells. To functionally address the role of BDNF in muscle satellite cells and regeneration in vivo, we generated a mouse in which BDNF is specifically depleted from skeletal muscle cells. For comparative purposes, and to determine the specific role of muscle-derived BDNF, we also examined muscles of the complete BDNF−/− mouse. In both models, expression of the satellite cell marker Pax7 was significantly decreased. Furthermore, proliferation and differentiation of primary myoblasts was abnormal, exhibiting delayed induction of several markers of differentiation as well as decreased myotube size. Treatment with exogenous BDNF protein was sufficient to rescue normal gene expression and myotube size. Because satellite cells are responsible for postnatal growth and repair of skeletal muscle, we next examined whether regenerative capacity was compromised. After injury, BDNF-depleted muscle showed delayed expression of several molecular markers of regeneration, as well as delayed appearance of newly regenerated fibers. Recovery of wild-type BDNF levels was sufficient to restore normal regeneration. Together, these findings suggest that BDNF plays an important role in regulating satellite cell function and regeneration in vivo, particularly during early stages.

scholarly journals Canonical NF-κB signaling regulates satellite stem cell homeostasis and function during regenerative myogenesis

2018 ◽  
Vol 11 (1) ◽  
pp. 53-66 ◽  
Author(s):  
Alex R Straughn ◽  
Sajedah M Hindi ◽  
Guangyan Xiong ◽  
Ashok Kumar
Keyword(s):  
Skeletal Muscle ◽  
Satellite Cell ◽  
Satellite Cells ◽  
Muscle Regeneration ◽  
Cell Function ◽  
Skeletal Muscle Regeneration ◽  
Cell Homeostasis ◽  
Adult Skeletal Muscle ◽  
Adult Mice ◽  
And Function

Abstract Skeletal muscle regeneration in adults is attributed to the presence of satellite stem cells that proliferate, differentiate, and eventually fuse with injured myofibers. However, the signaling mechanisms that regulate satellite cell homeostasis and function remain less understood. While IKKβ-mediated canonical NF-κB signaling has been implicated in the regulation of myogenesis and skeletal muscle mass, its role in the regulation of satellite cell function during muscle regeneration has not been fully elucidated. Here, we report that canonical NF-κB signaling is induced in skeletal muscle upon injury. Satellite cell-specific inducible ablation of IKKβ attenuates skeletal muscle regeneration in adult mice. Targeted ablation of IKKβ also reduces the number of satellite cells in injured skeletal muscle of adult mice, potentially through inhibiting their proliferation and survival. We also demonstrate that the inhibition of specific components of the canonical NF-κB pathway causes precocious differentiation of cultured satellite cells both ex vivo and in vitro. Finally, our results highlight that the constitutive activation of canonical NF-κB signaling in satellite cells also attenuates skeletal muscle regeneration following injury in adult mice. Collectively, our study demonstrates that the proper regulation of canonical NF-κB signaling is important for the regeneration of adult skeletal muscle.

scholarly journals Effects of Testosterone Supplementation on Skeletal Muscle Fiber Hypertrophy and Satellite Cells in Community-Dwelling Older Men

2006 ◽  
Vol 91 (8) ◽  
pp. 3024-3033 ◽  
Author(s):  
Indrani Sinha-Hikim ◽  
Marcia Cornford ◽  
Hilda Gaytan ◽  
Martin L. Lee ◽  
Shalender Bhasin
Keyword(s):  
Skeletal Muscle ◽  
Satellite Cell ◽  
Muscle Fiber ◽  
Satellite Cells ◽  
Older Men ◽  
Cell Number ◽  
Community Dwelling ◽  
Testosterone Treatment ◽  
Testosterone Administration ◽  
Dose Dependent

Abstract Objective: In this study, we determined the effects of graded doses of testosterone on muscle fiber cross-sectional area (CSA) and satellite cell number and replication in older men. Participants: Healthy men, 60–75 yr old, received a long-acting GnRH agonist to suppress endogenous testosterone production and 25, 50, 125, 300, or 600 mg testosterone enanthate im weekly for 20 wk. Methods: Immunohistochemistry, light and confocal microscopy, and electron microscopy were used to perform fiber typing and quantitate myonuclear and satellite cell number in vastus lateralis biopsies, obtained before and after 20 wk of treatment. Results: Testosterone administration in older men was associated with dose-dependent increases in CSA of both types I and II fibers. Satellite cell number increased dose dependently at the three highest doses (3% at baseline vs. 6.2, 9.2, and 13.0% at 125, 300, and 600 mg doses, P < 0.05). Testosterone administration was associated with an increase in the number of proliferating cell nuclear antigen+ satellite cells (1.8% at baseline vs. 3.9, 7.5, and 13% at 125, 300, and 600 mg doses, P < 0.005). The expression of activated Notch, examined only in the 300-mg group (baseline, 2.3 vs. 9.0% after treatment, P < 0.005), increased in satellite cells after testosterone treatment. The expression of myogenin (baseline, 6.2 vs. 20.7% after treatment, P < 0.005), examined only in the 300-mg group, increased significantly in muscle fiber nuclei after testosterone treatment, but Numb expression did not change. Conclusions: Older men respond to graded doses of testosterone with a dose-dependent increase in muscle fiber CSA and satellite cell number. Testosterone-induced skeletal muscle hypertrophy in older men is associated with increased satellite cell replication and activation.

scholarly journals Expression of Cd34 and Myf5 Defines the Majority of Quiescent Adult Skeletal Muscle Satellite Cells

2000 ◽  
Vol 151 (6) ◽  
pp. 1221-1234 ◽  
Author(s):  
Jonathan R. Beauchamp ◽  
Louise Heslop ◽  
David S.W. Yu ◽  
Shahragim Tajbakhsh ◽  
Robert G. Kelly ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Satellite Cell ◽  
Satellite Cells ◽  
Myosin Light Chain ◽  
Cell Activation ◽  
Cell Marker ◽  
Alternate Splicing ◽  
Adult Skeletal Muscle ◽  
Hematopoietic Stem ◽  
Cell Quiescence

Skeletal muscle is one of a several adult post-mitotic tissues that retain the capacity to regenerate. This relies on a population of quiescent precursors, termed satellite cells. Here we describe two novel markers of quiescent satellite cells: CD34, an established marker of hematopoietic stem cells, and Myf5, the earliest marker of myogenic commitment. CD34+ve myoblasts can be detected in proliferating C2C12 cultures. In differentiating cultures, CD34+ve cells do not fuse into myotubes, nor express MyoD. Using isolated myofibers as a model of synchronous precursor cell activation, we show that quiescent satellite cells express CD34. An early feature of their activation is alternate splicing followed by complete transcriptional shutdown of CD34. This data implicates CD34 in the maintenance of satellite cell quiescence. In heterozygous Myf5nlacZ/+ mice, all CD34+ve satellite cells also express β-galactosidase, a marker of activation of Myf5, showing that quiescent satellite cells are committed to myogenesis. All such cells are positive for the accepted satellite cell marker, M-cadherin. We also show that satellite cells can be identified on isolated myofibers of the myosin light chain 3F-nlacZ-2E mouse as those that do not express the transgene. The numbers of satellite cells detected in this way are significantly greater than those identified by the other three markers. We conclude that the expression of CD34, Myf5, and M-cadherin defines quiescent, committed precursors and speculate that the CD34−ve, Myf5−ve minority may be involved in maintaining the lineage-committed majority.

Myogenic satellite cells: physiology to molecular biology

2001 ◽  
Vol 91 (2) ◽  
pp. 534-551 ◽  
Author(s):  
Thomas J. Hawke ◽  
Daniel J. Garry
Keyword(s):  
Skeletal Muscle ◽  
Satellite Cell ◽  
Cell Population ◽  
Satellite Cells ◽  
Cell Biology ◽  
Transgenic Animal ◽  
Future Research ◽  
Adult Skeletal Muscle ◽  
Cell Culture Techniques ◽  
Culture Techniques

Adult skeletal muscle has a remarkable ability to regenerate following myotrauma. Because adult myofibers are terminally differentiated, the regeneration of skeletal muscle is largely dependent on a small population of resident cells termed satellite cells. Although this population of cells was identified 40 years ago, little is known regarding the molecular phenotype or regulation of the satellite cell. The use of cell culture techniques and transgenic animal models has improved our understanding of this unique cell population; however, the capacity and potential of these cells remain ill-defined. This review will highlight the origin and unique markers of the satellite cell population, the regulation by growth factors, and the response to physiological and pathological stimuli. We conclude by highlighting the potential therapeutic uses of satellite cells and identifying future research goals for the study of satellite cell biology.

scholarly journals Satellite cell depletion does not inhibit adult skeletal muscle regrowth following unloading-induced atrophy

2012 ◽  
Vol 303 (8) ◽  
pp. C854-C861 ◽  
Author(s):  
Janna R. Jackson ◽  
Jyothi Mula ◽  
Tyler J. Kirby ◽  
Christopher S. Fry ◽  
Jonah D. Lee ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Satellite Cell ◽  
Muscle Atrophy ◽  
Soleus Muscle ◽  
Satellite Cells ◽  
Muscle Fibers ◽  
Domain Size ◽  
Adult Skeletal Muscle ◽  
Muscle Plasticity ◽  
Myonuclear Domain

Resident muscle stem cells, known as satellite cells, are thought to be the main mediators of skeletal muscle plasticity. Satellite cells are activated, replicate, and fuse into existing muscle fibers in response to both muscle injury and mechanical load. It is generally well-accepted that satellite cells participate in postnatal growth, hypertrophy, and muscle regeneration following injury; however, their role in muscle regrowth following an atrophic stimulus remains equivocal. The current study employed a genetic mouse model (Pax7-DTA) that allowed for the effective depletion of >90% of satellite cells in adult muscle upon the administration of tamoxifen. Vehicle and tamoxifen-treated young adult female mice were either hindlimb suspended for 14 days to induce muscle atrophy or hindlimb suspended for 14 days followed by 14 days of reloading to allow regrowth, or they remained ambulatory for the duration of the experimental protocol. Additionally, 5-bromo-2′-deoxyuridine (BrdU) was added to the drinking water to track cell proliferation. Soleus muscle atrophy, as measured by whole muscle wet weight, fiber cross-sectional area, and single-fiber width, occurred in response to suspension and did not differ between satellite cell-depleted and control muscles. Furthermore, the depletion of satellite cells did not attenuate muscle mass or force recovery during the 14-day reloading period, suggesting that satellite cells are not required for muscle regrowth. Myonuclear number was not altered during either the suspension or the reloading period in soleus muscle fibers from vehicle-treated or satellite cell-depleted animals. Thus, myonuclear domain size was reduced following suspension due to decreased cytoplasmic volume and was completely restored following reloading, independent of the presence of satellite cells. These results provide convincing evidence that satellite cells are not required for muscle regrowth following atrophy and that, instead, the myonuclear domain size changes as myofibers adapt.

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